From mitochondrial dysregulation to ferroptosis: Exploring new strategies and challenges in radioimmunotherapy (Review).

Abstract

Ferroptosis is an iron‑dependent, lipid peroxidation‑driven form of regulated immunogenic cell death (ICD). ICD has demonstrated potential to overcome resistance to conventional cancer therapies, enhancing the efficacy of treatments such as chemotherapy, radiotherapy, immunotherapy and photodynamic therapy. Notably, in the context of radiotherapy, ferroptosis serves a key role, particularly when combined with radioimmunotherapy. Mitochondria are central to the regulation of radiation‑induced oxidative stress and the remodeling of the immune microenvironment, and they undergo characteristic morphological changes during the ferroptotic process. However, the precise regulatory association between mitochondrial dysfunction and ferroptosis remains incompletely understood, and there is an ongoing debate regarding this complex interaction. The present review aimed to explore the mechanisms through which mitochondria and ferroptosis interact in the context of radiotherapy, with a focus on how ferroptosis exacerbates mitochondrial dysfunction. Additionally, the present review proposed novel strategies leveraging radioimmunotherapy to offer more precise and effective approaches for cancer treatment.